Positive inotropic effect of exogenous and endogenous NO in hypertrophic rat hearts

1 Recent evidence suggests that nitric oxide (NO) modulates the contractile force of isolated cardiomyocytes in a biphasic manner. We sought to examine whether myocardial hypertrophy induced by long‐term hypertension changes the effects of NO on myocardial contractility. 2 We used constant flow perfused non‐paced Langendorff preparations of hearts of 3 months old Wistar rats (WIS, n =23) and of stroke‐prone spontaneously hypertensive rats (SHR) at the age of 10 months (SHR10, n =16) and 15 months (SHR15, n =8). Changes of left ventricular peak pressure (LVP), +dP/dt max , −dP/dt max , coronary perfusion pressure (CPP) and heart rate (HR) were recorded after infusion of noradrenaline (NA, 0.1 μmol  l −1 ), glyceryl trinitrate (GTN, 1–100 μmol 1 −1 ), S‐nitroso‐ N ‐acetyl‐ D , L ‐penicillamine (SNAP, 1–10 μmol 1 −1 ) and N ω ‐nitro‐ L ‐arginine ( L ‐NOARG, 0.1–1 mmol 1 −1 ). 3 Long‐term hypertension induced myocardial hypertrophy and an abnormal response to NA. The relative heart weight (in mg kg −1 ) increased from 2.95±0.04 (WIS) to 6.67±0.34 (SHR15), while the increase in +dP/dt max induced by NA was absent in SHR15. Hearts of SHR10 showed an intermediate response. 4 Both SNAP and GTN significantly increased LVP, +dP/dt max and −dP/dt max in hearts of WIS and of SHR. In WIS but not in SHR10, SNAP also increased HR. In SHR10 the lowest concentration of SNAP (1 μmol 1 −1 ) showed no effect on contractility but a significantly diminished reduction of CPP suggesting inactivation of extracellularly released NO in the coronary circulation of SHR. 5 L ‐NOARG significantly reduced contractility in hearts of WIS and of SHR to a similar extent. At a concentration of 1 mmol 1 −1   L ‐NOARG also reduced HR. 6 These results suggests that positive inotropic effects of exogenous and endogenous NO are not changed in hypertension induced myocardial hypertrophy.British Journal of Pharmacology (1997) 122 , 813–820; doi: 10.1038/sj.bjp.0701446